We are producing a collection of hybrid cell lines secreting monoclonal antibodies. These lines are prepared by hybridizing mouse plasmacytomas with spleen cells from a mouse immunized with human cells. The hybrid clones are screened for production of antibody directed against human tumor specific antigens and differentiation antigens. By using immunization protocols which reduce the production of background mouse anti-human antibodies we can obtain several clones making the desired antibody. These can be then grown in culture or passaged as tumors in mice and large amounts of monoclonal antibodies collected from the culture supernatant or mouse ascites fluid. We are concentrating on the production of antibodies against human leukemia specific antigens and lymphoid differentiation antigens. These monospecific reagents are being used for detection of the antigens on mouse-human hybrids and thus for the chromosomal localization of the genes for the antigens as well as for the isolation and characterization of the antigens.